Anti-CD40 Antibody Engineering for Affinity and Immune Modulation
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Solution Overview
Problem
There is a need for anti-CD40 antibodies with improved pharmaceutical characteristics, such as higher binding affinity and activity compared to existing antibodies like Dacetuzumab and Selicrelumab, for the treatment of cancers, infectious diseases, and autoimmune diseases.
Innovation Solution
Development of isolated monoclonal antibodies, including mouse, chimeric, and humanized antibodies, or their antigen-binding portions, with specific VH and VL CDR sequences that exhibit high affinity and functionality for CD40, and the creation of immunoconjugates, bispecific molecules, and chimeric antigen receptors to modulate immune responses and treat diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-CD40 antibodies (Dacetuzumab, Selicrelumab) are used, then CD40 signaling can be modulated, but binding affinity and activity are insufficient compared to the new antibody
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody's amino acid sequence, particularly in the CDR regions, to achieve higher binding affinity to CD40. The new antibody exhibits at least 10-fold higher binding affinity compared to existing antibodies through systematic optimization of binding parameters
2Object-affected harmful factors
If CD40-CD40L binding is blocked, then immune activation is reduced, but therapeutic effect against tumors and autoimmune diseases is diminished
Solution Approach 1:
The patent applies local quality by creating different antibody variants with specific functional properties. The antibody is engineered to selectively block pathological CD40-CD40L interactions while preserving or enhancing therapeutic immune activation through localized modifications in the binding interface
3Productivity
If CD40 signaling is activated, then immune response is enhanced, but risk of autoimmune reactions increases
Solution Approach 1:
The patent applies dynamics by creating a tunable antibody system where the degree of CD40 signaling activation can be controlled. The antibody provides dynamic immune modulation, enhancing anti-tumor responses while maintaining control over autoimmune reactions through adjustable binding characteristics
Data Source
AI summary
Provided is an isolated monoclonal antibody or an antigen-binding portion thereof that specifically binds human CD40. A nucleic acid molecule encoding the antibody or antigen-binding portion thereof, an expression vector, a host cell and a method for expressing the antibody or the antigen-binding portion thereof are also provided. An immunoconjugate, a bispecific molecule, a chimeric antigen receptor, an oncolytic virus and a pharmaceutical composition comprising the antibody or antigen-binding portion thereof, as well as a treatment method using the same are further provided.